Caspase-3-associated apoptotic cell death in excitotoxic necrosis of the entorhinal cortex following intraperitoneal injection of kainic acid in the rat
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Caspase-3-associated apoptotic cell death in excitotoxic necrosis of the entorhinal cortex following intraperitoneal injection of kainic acid in the rat. / Puig, B; Ferrer, I; Puig Martorell, Berta.
In: NEUROSCI LETT, Vol. 321, No. 3, 22.03.2002, p. 182-6.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Caspase-3-associated apoptotic cell death in excitotoxic necrosis of the entorhinal cortex following intraperitoneal injection of kainic acid in the rat
AU - Puig, B
AU - Ferrer, I
AU - Puig Martorell, Berta
PY - 2002/3/22
Y1 - 2002/3/22
N2 - The present study is directed to study: (a) bax translocation and cytochrome c release as mediators of the mitochondrial pathway of apoptosis; (b) Fas-L (Fas-ligand) expression as an indicator of the possible involvement of the Fas/Fas-L signaling pathway; and (c) active caspase-3 expression as the main executioner of caspase-mediated apoptosis, in rats receiving an intraperitoneal injection of the glutamate analogue kainic acid (KA) at a dose of 9 mg/kg, which is sufficient to produce generalized seizures and excitotoxic cell death in the entorhinal cortex. Sub-fractionation studies of entorhinal cortex homogenates have shown cytochrome c and cytochrome oxidase IV localized in the mitochondrial fraction, and Bax localized in the cytosolic fraction. No modifications in the sub-cellular distribution of cytochrome c and Bax have been observed at 6 h and 24 h in KA-treated rats. Morphological studies have shown cytoplasmic shrinkage and nuclear condensation consistent with necrosis in the entorhinal cortex. Many neurons (about 30% of dying cells) are stained with the method of in situ end-labeling of nuclear DNA fragmentation. Yet only about 5% of dying cells have apoptotic morphology. A percentage of dying cells (5% at 6 h and 40% at 24 h) over-express Fas-L but only about 2% of dying cells at 24 h post-injection express cleaved caspase-3 (17 kD). The present data further support the concept that necrosis is the predominant form of cell death in the entorhinal cortex, although caspase-3-dependent apoptotic cell death may play a limited role, in the present paradigm of KA-induced excitotoxicity.
AB - The present study is directed to study: (a) bax translocation and cytochrome c release as mediators of the mitochondrial pathway of apoptosis; (b) Fas-L (Fas-ligand) expression as an indicator of the possible involvement of the Fas/Fas-L signaling pathway; and (c) active caspase-3 expression as the main executioner of caspase-mediated apoptosis, in rats receiving an intraperitoneal injection of the glutamate analogue kainic acid (KA) at a dose of 9 mg/kg, which is sufficient to produce generalized seizures and excitotoxic cell death in the entorhinal cortex. Sub-fractionation studies of entorhinal cortex homogenates have shown cytochrome c and cytochrome oxidase IV localized in the mitochondrial fraction, and Bax localized in the cytosolic fraction. No modifications in the sub-cellular distribution of cytochrome c and Bax have been observed at 6 h and 24 h in KA-treated rats. Morphological studies have shown cytoplasmic shrinkage and nuclear condensation consistent with necrosis in the entorhinal cortex. Many neurons (about 30% of dying cells) are stained with the method of in situ end-labeling of nuclear DNA fragmentation. Yet only about 5% of dying cells have apoptotic morphology. A percentage of dying cells (5% at 6 h and 40% at 24 h) over-express Fas-L but only about 2% of dying cells at 24 h post-injection express cleaved caspase-3 (17 kD). The present data further support the concept that necrosis is the predominant form of cell death in the entorhinal cortex, although caspase-3-dependent apoptotic cell death may play a limited role, in the present paradigm of KA-induced excitotoxicity.
KW - Animals
KW - Apoptosis
KW - Caspase 3
KW - Caspases
KW - Cytochrome c Group
KW - Entorhinal Cortex
KW - Fas Ligand Protein
KW - Female
KW - Glutamic Acid
KW - Kainic Acid
KW - Membrane Glycoproteins
KW - Mitochondria
KW - Necrosis
KW - Neurons
KW - Neurotoxins
KW - Protein Transport
KW - Proto-Oncogene Proteins
KW - Proto-Oncogene Proteins c-bcl-2
KW - Rats
KW - Rats, Sprague-Dawley
KW - Signal Transduction
KW - bcl-2-Associated X Protein
M3 - SCORING: Journal article
C2 - 11880202
VL - 321
SP - 182
EP - 186
JO - NEUROSCI LETT
JF - NEUROSCI LETT
SN - 0304-3940
IS - 3
ER -